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Interleukin-1 and interleukin-1 receptor antagonist
1Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
Nutrition (Burbank, Los Angeles County, Calif.)
|September 1, 1995
Summary
Blocking pro-inflammatory cytokines like Interleukin 1 (IL-1) and tumor necrosis factor (TNF) can reduce disease severity. Therapies targeting IL-1 and TNF show promise in treating inflammatory conditions and septic shock.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Cytokines, including Interleukin 1 (IL-1) and tumor necrosis factor (TNF), play critical roles in immune responses and inflammation.
- Pro-inflammatory cytokines IL-1 and TNF can exacerbate disease processes, affecting numerous cell types.
- Naturally occurring antagonists and soluble receptors for IL-1 and TNF exist, but their sufficiency in blocking disease-related cytokine activity is unclear.
Purpose of the Study:
- To review the role of blocking Interleukin 1 (IL-1) and tumor necrosis factor (TNF) in disease models.
- To evaluate the efficacy of IL-1 receptor antagonist (IL-1ra) and anti-TNF therapies in reducing inflammation and mortality.
- To investigate the endogenous production of IL-1ra and soluble TNF receptors during disease and therapeutic interventions.
Main Methods:
- Utilizing animal models of infectious, inflammatory, and metastatic diseases to study cytokine blockade.
- Employing anti-TNF monoclonal antibodies and soluble receptors to assess TNF inhibition.
- Administering antibodies to the type I IL receptor, IL-1 receptor antagonist (IL-1ra), and soluble IL-1 receptor for IL-1 pathway blockade.
- Analyzing data from a Phase III trial of IL-1ra in septic shock patients.
Main Results:
- Anti-TNF therapies (monoclonal antibodies, soluble receptors) have demonstrated reductions in inflammation and lethality in animal models.
- IL-1ra and soluble IL-1 receptor interventions have shown efficacy in mitigating disease severity across various inflammatory models.
- A Phase III trial indicated that IL-1ra reduced mortality by 22% in patients with septic shock syndrome.
- Infusion of IL-1 or TNF in patients induced circulating levels of their respective antagonists (IL-1ra) or soluble receptors, but not the cytokines themselves.
Conclusions:
- Targeting pro-inflammatory cytokines IL-1 and TNF with specific antagonists or blocking agents is a viable therapeutic strategy.
- IL-1ra has shown significant potential in reducing mortality in severe conditions like septic shock.
- Further research is needed to determine if endogenous levels of IL-1ra and soluble TNF receptors are sufficient to counteract cytokine-driven inflammation in disease states.